Treatment of Older Patients with Mantle-Cell Lymphoma

BACKGROUND: The long-term prognosis for older patients with mantle-cell lymphoma is poor. Chemoimmunotherapy results in low rates of complete remission, and most patients have a relapse. We investigated whether a fludarabine-containing induction regimen improved the complete-remission rate and whether maintenance therapy with rituximab prolonged remission. METHODS: We randomly assigned patients 60 years of age or older with mantle-cell lymphoma, stage II to IV, who were not eligible for high-dose therapy to six cycles of rituximab, fludarabine, and cyclophosphamide (R-FC) every 28 days or to eight cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) every 21 days. Patients who had a response underwent a second randomization to maintenance therapy with rituximab or interferon alfa, each given until progression. RESULTS: Of the 560 patients enrolled, 532 were included in the intention-to-treat analysis for response, and 485 in the primary analysis for response. The median age was 70 years. Although complete-remission rates were similar with R-FC and R-CHOP (40% and 34%, respectively; P=0.10), progressive disease was more frequent with R-FC (14%, vs. 5% with R-CHOP). Overall survival was significantly shorter with R-FC than with R-CHOP (4-year survival rate, 47% vs. 62%; P=0.005), and more patients in the R-FC group died during the first remission (10% vs. 4%). Hematologic toxic effects occurred more frequently in the R-FC group than in the R-CHOP group, but the frequency of grade 3 or 4 infections was balanced (17% and 14%, respectively). In 274 of the 316 patients who were randomly assigned to maintenance therapy, rituximab reduced the risk of progression or death by 45% (in remission after 4 years, 58%, vs. 29% with interferon alfa; hazard ratio for progression or death, 0.55; 95% confidence interval, 0.36 to 0.87; P=0.01). Among patients who had a response to R-CHOP, maintenance therapy with rituximab significantly improved overall survival (4-year survival rate, 87%, vs. 63% with interferon alfa; P=0.005). CONCLUSIONS: R-CHOP induction followed by maintenance therapy with rituximab is effective for older patients with mantle-cell lymphom

Treatment of Older Patients With Mantle Cell Lymphoma (MCL):Long-Term Follow-Up of the Randomized European MCL Elderly Trial

PURPOSE: In an update of the randomized, open-label, phase III European Mantle Cell Lymphoma (MCL) Elderly trial (ClinicalTrials.gov identifier: NCT00209209), published in 2012, we aimed to confirm results on long-term outcome focusing on efficacy and safety of long-term use of rituximab maintenance. PATIENTS AND METHODS: Five hundred sixty patients with newly diagnosed MCL underwent a first random assignment between rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and rituximab, fludarabine, and cyclophosphamide (R-FC) induction, followed by a second random assignment in 316 responders between rituximab and interferon alfa maintenance, to be continued until progression. We compared progression-free survival from the second randomization and overall survival (OS) from the first or second randomizations. RESULTS: After a median follow-up time of 7.6 years, the previously described difference in OS between the induction arms persisted (median, 6.4 years after R-CHOP [n = 280] v 3.9 years after R-FC [n = 280]; P = .0054). Patients responding to R-CHOP had median progression-free survival and OS times of 5.4 and 9.8 years, respectively, when randomly assigned to rituximab (n = 87), compared with 1.9 years (P < .001) and 7.1 years (P = .0026), respectively, when randomly assigned to interferon alfa (n = 97). In 58% and 32% of patients treated with R-CHOP, rituximab maintenance was still ongoing 2 and 5 years from start of maintenance, respectively. After R-FC, rituximab maintenance was associated with an unexpectedly high cumulative incidence of death in remission (22% at 5 years). Toxicity of rituximab maintenance was low after R-CHOP (grade 3-4 leukopenia or infection < 5%) but more prominent in patients on rituximab maintenance after R-FC, in whom grade 3-4 leukopenia (up to 40%) and infections were frequent (up to 15%). CONCLUSION: The excellent results of R-CHOP followed by rituximab maintenance until progression for older patients with MCL persisted in a mature follow-up. Prolongation of rituximab maintenance beyond 2 years is effective and safe

Treatment of limited stage follicular lymphoma with Rituximab immunotherapy and involved field radiotherapy in a prospective multicenter Phase II trial-MIR trial

<p>Abstract</p> <p>Background</p> <p>The optimal treatment of early stage follicular Lymphoma is a matter of debate. Radiation therapy has frequently been applied with a curative approach beside watchful waiting. Involved field, extended field and total nodal radiation techniques are used in various protocols, but the optimal radiation field still has to be defined. Follicular lymphoma is characterized by stable expression of the CD20 antigen on the tumour cells surface. The anti CD20 antibody Rituximab (Mabthera^®) has shown to be effective in systemic therapy of FL in primary treatment, relapse and maintenance therapy.</p> <p>Methods/design</p> <p>The MIR (Mabthera^®and Involved field Radiation) study is a prospective multicenter trial combining systemic treatment with the anti CD20 antibody Rituximab (Mabthera^®) in combination with involved field radiotherapy (30 - 40 Gy). This trial aims at testing the combination's efficacy and safety with an accrual of 85 patients.</p> <p>Primary endpoint of the study is progression free survival. Secondary endpoints are response rate to Rituximab, complete remission rate at week 18, relapse rate, relapse pattern, relapse free survival, overall survival, toxicity and quality of life.</p> <p>Discussion</p> <p>The trial evaluates the efficacy of Rituximab to prevent out-filed recurrences in early stage nodal follicular lymphoma and the safety of the combination of Rituximab and involved field radiotherapy. It also might show additional risk factors for a later recurrence (e.g. remission state after Rituximab only).</p> <p>Trial Registration</p> <p>ClinicalTrials (NCT): <a href="http://www.clinicaltrials.gov/ct2/show/NCT00509184">NCT00509184</a></p

ИССЛЕДОВАНИЕ И ОПИСАНИЕ БЫТОВЫХ ГАЗОВЫХ СЧЕТЧИКОВ

В работе описывается исследование бытовых газовых счетчиков, их разновидности по принципу действия, основные преимущества и их метрологические характеристики. А также рассмотрены характеристики природного газа

Ki-67 as a prognostic marker in mantle cell lymphoma—consensus guidelines of the pathology panel of the European MCL Network

Mantle cell lymphoma (MCL) has a heterogeneous clinical course and is mainly an aggressive B cell non-Hodgkin lymphoma; however, there are some indolent cases The Ki-67 index, defined by the percentage of Ki-67-positive lymphoma cells on histopathological slides, has been shown to be a very powerful prognostic biomarker. The pathology panel of the European MCL Network evaluated methods to assess the Ki-67 index including stringent counting, digital image analysis, and estimation by eyeballing. Counting of 2 × 500 lymphoma cells is the gold standard to assess the Ki-67 index since this value has been shown to predict survival in prospective randomized trials of the European MCL Network. Estimation by eyeballing and digital image analysis showed a poor concordance with the gold standard (concordance correlation coefficients [CCC] between 0.29 and 0.61 for eyeballing and CCC of 0.24 and 0.37 for two methods of digital image analysis, respectively). Counting a reduced number of lymphoma cells (2 × 100 cells) showed high interobserver agreement (CCC = 0.74). Pitfalls of the Ki-67 index are discussed and guidelines and recommendations for assessing the Ki-67 index in MCL are given

Sum Frequency Generation Spectroscopy on Platinum and Palladium Model Catalysts

Titel, Danksagung Abkürzungen Inhaltsverzeichnis 1 Einleitung 1 2 Theorie der SFG an Oberflächen 5 3 Apparativer Aufbau und Experimentelles 33 4 Messungen an Pt(111) 61 5 Messungen an Pd(111) 67 6 Messungen an Pd/Al2O3/NiAl(110) 93 7 Polarisationsabhängige Messungen 161 8 Reaktionen 177 9 Zusammenfassung 189 Anhang 193 Literaturverzeichnis 233Summenfrequenzerzeugungsspektroskopie (SFG) ist eine nichtlinear optische, oberflächensensitive und druckunabhängige Methode, welche die Aufnahme von Schwingungsspektren im Druckbereich vom Ultrahochvakuum (UHV) bis zu etwa 1 bar ermöglicht. Im Rahmen dieser Dissertation wurden zur Präparation und Untersuchung von Modellkatalysatoren eine Ultrahochvakuumkammer mit Hochdruckzelle und zwei SFG-Spektrometer entwickelt, die auf unterschiedlichen Pikosekundenlasersystemen (Ti:Sa bzw. Nd:YAG) basieren. Die Eignung der Instrumentation wurde mit der Untersuchung der Adsorption von Kohlenmonoxid und Ethylen auf einer Vielzahl von Modellkatalysatoren in Gasphasen des genannten Druckbereichs und unter Reaktionsbedingungen demonstriert. In SFG-Spektren von CO/Pt(111) wurden bei Drücken bis zu 500 mbar keine Hochdruckspezies detektiert - im Gegensatz zu Ergebnissen anderer Arbeitsgruppen. Es wird ausführlich auf die Notwendigkeit einer Gasphasenkompensation eingegangen. Umfassende Messungen am System CO/Pd(111) bis 1000 mbar ergaben, daß die Adsorbatstrukturen, die bei tiefen Temperaturen im Hochvakuum präpariert werden, auch bei hohen Oberflächentemperaturen erzeugt werden können - bei entsprechend hohen Drücken. Bei der Bestimmung des Neigungswinkels von CO auf der Pd(111)-Oberfläche in polarisationsabhängigen Messungen ergab sich eine starke Modellabhängigkeit. Bei ersten SFG-Messungen der CO-Adsorption auf geträgerten Palladium- Nanoteilchen (Pd/Al2O3/NiAl(110)) verschiedener Größe (< 10 nm) und Morphologie mit dem Ti:Sa-Spektrometer fand sich im Hochvakuum auf ungeordneten Partikeln gegenüber facettierten Partikeln ein größeres on-top- Signal. Das Signal des bridge-CO auf beiden Sorten von Nanoteilchen entsprach in seiner Frequenz eher dem defektreicher Pd(111)-Oberflächen. Bei hohen Drücken von einigen hundert mbar konnte eine stärkere Bevölkerung der on-top- Plätze auch auf den facettierten Partikeln erreicht werden. Mit dem besser auflösenden Nd:YAG-Spektrometer wurde auf facettierten Partikeln im Hochvakuum wie bei hohen Drücken zusätzlich ein hollow-Signal und eine zweite bridge- Spezies, die dem CO auf (111)-Facetten zugeordnet wurde, nachgewiesen. In den Spektren facettierter Partikel wurde damit eine Komponente identifiziert, die sich im Hochvakuum bei tiefen Temperaturen und unter Hochdruck analog CO/Pd(111) verhält. Unterschiede zur Pd(111)-Oberfläche sind in der Heterogenität der Partikel begründet. Die Nanopartikelspektren der beiden Spektrometer zeigten unterschiedliche Linienformen (Absorptions- bzw. Dispersionskurven). Dies ist Folge des Unterschieds im nichtresonanten Hintergrund, der wahrscheinlich in den verschiedenen (vis-)Laserwellenlängen begründet ist. In Messungen mit dem Nd:YAG-Spektrometer fand sich außerdem eine Abhängigkeit der Linienform von der verwendeten Polarisationskombination (ppp bzw. ssp). Die Eignung des experimentellen Aufbaus für die Untersuchung heterogener Reaktionen mit SFG-Spektroskopie und gleichzeitiger gaschromatographischer Gasphasenanalyse wurde anhand der CO-Hydrierung und der Ethylenhydrierung gezeigt.Sum frequency generation spectroscopy (SFG) is a nonlinear optical, surface sensitive and pressure independent method allowing to acquire vibrational spectra in a pressure range from ultrahigh vacuum (UHV) up to about 1 bar. During this thesis work an ultrahigh vacuum chamber with high pressure cell and two SFG spectrometers based on different picosecond laser systems (Ti:Sa and Nd:YAG) were developed for preparation and investigation of model catalysts. The suitability of the setup was demonstrated in studies of the adsorption of carbon monoxide and ethylene on a multitude of model catalysts in the pressure range mentioned above and under reaction conditions. In SFG spectra of the system CO/Pt(111) at pressures up to 500 mbar no high pressure species were detected - contrary to results obtained by other groups. The necessity of performing a compensation for gas-phase absorption is treated in detail. Extensive measurements of CO/Pd(111) up to 1000 mbar showed, that adsorbate structures prepared at low temperatures in high vacuum can also be obtained at high surface temperatures - at accordingly high pressures. Determination of the tilt angle of CO on Pd(111) in polarization dependent measurements showed a strong dependency on the model used. In first SFG measurements of CO adsorption on supported Palladium nanoparticles (Pd/Al2O3/NiAl(110)) of different size (< 10 nm) and morphology with the Ti:Sa spectrometer, in high vacuum the signal of on-top CO on disordered particles was bigger than that on faceted particles. The frequency of the bridge signal on both kinds of nanoparticles corresponded to that found on defective Pd(111) surfaces. At high pressures of a few hundred mbar a higher population of on-top sites could be reached also for the faceted particles. With the better resolution of the Nd:YAG spectrometer in addition hollow CO and a second bridge species attributed to CO on (111) facets were detected on faceted particles, in high vacuum and at high pressure. Thus, in spectra of faceted particles a component was identified that behaves in high vacuum at low temperatures and at high pressure analogously to CO/Pd(111). Differences to the Pd(111) surface are caused by the heterogeneity of the particles. The nanoparticle spectra recorded with the two spectrometers showed different lineshapes (absorption vs. dispersion curves). This results from the difference in the non resonant background, that is probably caused by the differing (vis-)laser wavelengths. In measurements with the Nd:YAG spectrometer also an dependency of the lineshape on the polarization combination (ppp or ssp) used was found. The suitability of the experimental setup for investigations of heterogeneous reactions with SFG spectroscopy and simultaneous gas-phase analysis by gas chromatography was demonstrated by measurements of CO hydrogenation and ethylene hydrogenation

Vibrational sum frequency spectroscopy on Pd(111) and supported Pd nanoparticles: CO adsorption from ultrahigh vacuum to atmospheric pressure

The adsorption of CO on Pd(I 11) and on Al2O3-supported Id nanoparticles was studied by picosecond infrared-visible sum frequency generation (SFG) vibrational spectroscopy in a pressure range from 10(-7) to 1000 mbar and in a temperature range of 100-520 K. Under ultrahigh vacuum (UHV), the samples were further characterized by low-energy electron diffraction (LEED), Auger electron spectroscopy (AES), and temperature-programmed desorption (TPD). Identical high coverage (saturation) CO structures were observed on Pd(l 11) under UHV conditions (10(-7) mbar, 100 K) and at high pressure (e.g., I mbar, 190 K). No indications of pressure-induced surface rearrangements of Pd(l 11) were evident from SFG and LEED. SFG spectra of CO adsorption on "defect-rich" Pd(l 11) revealed an additional peak that was attributed to adsorption on defect (step or edge) sites. The CO adsorbate structure on supported Pd nanoparticles was found to be different from that on Pd(I 11) and to be more similar to that on stepped or strongly sputtered Pd( I I I), At low pressure, the adsorption site occupancy depended on the particle surface structure and temperature. CO preferentially adsorbed in bridge sites on well-faceted Pd particles, while on more defective Pd particles, on-top sites were occupied as well. However, at 200 mbar CO, an adsorption site occupancy was obtained that was nearly independent of the particle surface structure. While the surface structure of the Pd particles remained unchanged upon high-pressure gas exposure, an annealing treatment to 300-400 K was able to order the Pd particle surface. Gas mixtures of CO and hydrogen on Pd(l 11) showed SFG spectra similar to the pure CO case indicating the absence of a strong interaction between CO and hydrogen

Nitraminanaloge Suosan-Derivate als potentielle Süßstoffe

Substituted phenylaminocarbonylaziridines are reacted with N-nitro-ethylcarbamate and then with ammonia to give N-aryl-N′-nitroaminoethyl-ureas 5-11 after acidification. 5 and 6 have a sweet taste, 7 is bitter

Aufnahme ausgewählter Metalle in Kompartimente von Solanaceen

The Uptake of several metals into the compartments of Atropa belladonna, Datura stramoni-um, and Hyoscyamus niger is measured by ICP-AES. In the roots the series AI &lt; Ba &lt; Cr &lt; Cu&lt; Zn &lt; Sr is observed

Zur Elementbestimmung in Solanaceen

The Contents of Al, Ba, Cr, Cu, Sr, and Zn in Atropa belladonna, Datura stramonium, and Hyoscyamus niger are measured by ICP-AES. Enrichment of these elements in the leaves is observed